JP2018524121A - Absorbable antibacterial wound dressing - Google Patents

Abstract

  The present invention is a method for preparing an absorbable antimicrobial wound dressing comprising the following steps: (a) mixing an antimicrobial agent and one or more polymers in a solvent system comprising a non-aqueous solvent. Preparing an antimicrobial coating composition, (b) contacting the antimicrobial coating composition of step (a) with a wound dressing substrate containing absorbent fibers or absorbent particles, and (c) step (b) And drying the product of). The present invention also provides an absorbent antimicrobial wound dressing comprising an absorbent antimicrobial wound dressing prepared by these methods, as well as an antimicrobial coating composition, and a method of making the antimicrobial coating composition.

Description

BACKGROUND OF THE INVENTION Wound dressings have been used for centuries to promote healing, protect damaged tissue from dirt and foreign body contamination, and protect from infection. Studies have shown that a moist environment helps promote wound healing. This has prompted the development of absorbent wound dressings that absorb and retain exudates. It may be desirable to include an antimicrobial agent in such an absorbent wound dressing to further prevent infection and promote wound healing. It may also be desirable to do so that the antimicrobial agent is evenly distributed within the dressing matrix. It may also be desirable for the antimicrobial agent to be stabilized against degradation over time.

SUMMARY OF THE INVENTION The present invention provides that certain antibacterial agents (eg, silver-based antibacterial agents) are soluble only in highly aqueous solutions, while polymers useful for the manufacture of absorbent wound dressings are In part, the recognition is that it is incompatible with highly aqueous solutions because it gels in the presence of water. Therefore, the application of antimicrobial agents that are only soluble in highly aqueous solutions to absorbent wound dressings that are incompatible with highly aqueous solutions has so far limited the development of absorbent antimicrobial wound dressings Bring real challenges.

  The present invention solves these and other problems by mixing an antimicrobial agent in a solvent system including a non-aqueous solvent and one or more polymers. While not wishing to be bound by theory, it is believed that a non-aqueous solvent avoids or reduces the amount of absorption that occurs during application of the antimicrobial agent, while one or more polymers reduce the dispersion of the antimicrobial agent. It is thought to help and prevent their settling. Accordingly, in one aspect, the present invention is a method for preparing an absorbable antimicrobial wound dressing comprising the following steps: (a) an antimicrobial agent and one or more polymers in a solvent system comprising a non-aqueous solvent. (B) contacting the antimicrobial coating composition of step (a) with a wound dressing substrate containing absorbent fibers or particles, and ( c) drying the product of step (b). The present invention also provides an absorbent antimicrobial wound dressing comprising an absorbent antimicrobial wound dressing prepared by these methods, as well as an antimicrobial coating composition, and a method of making the antimicrobial coating composition.

  As discussed below, in some embodiments, one or more polymers in the antimicrobial coating on the wound dressing substrate modulate the rate at which the antimicrobial agent is released from the resulting wound dressing. Thus, in some embodiments, the rate of release of the antimicrobial agent from the wound dressing is achieved by changing the amount of one or more polymers mixed with the antimicrobial agent and / or different polymers, polymers of different molecular weights, Or it can be fine-tuned by using a combination of different polymers. While the methods of the present invention are particularly useful for antimicrobial agents that are soluble only in highly aqueous solutions (eg, silver-based antimicrobial agents), the ability to control the release rate of antimicrobial agents is not It also means that it can be useful for antibacterial agents that are soluble in aqueous solvents (eg, PHMB). A further advantage of the present invention is that, in some embodiments, wound dressings prepared according to the methods described herein, particularly wound dressings comprising a silver-based antimicrobial agent, over time as compared to existing antimicrobial wound dressings. This indicates that there is less discoloration. Another advantage of the present invention is that the antimicrobial coating compositions described herein also serve to hydrophilize the wound dressing substrates to which they are applied, eliminating the need for a separate hydrophilization step.

FIG. 1 illustrates the effect of changing HPC concentration on the amount of silver released from a wound dressing over time, according to some embodiments of the present invention. FIG. 2 illustrates steps in a method for providing an antimicrobial (AM) wound dressing according to some embodiments of the present invention. FIG. 3 shows the particle size distribution (in μm) of superabsorbent particles (SAP) useful for the preparation of wound dressings, according to some embodiments of the present invention. FIG. 4 illustrates the discoloration of a wound dressing substrate over time according to some embodiments of the present invention. FIG. 5A is a scanning electron micrograph image (LSEI detection at 1000 × magnification, 30 Pa pressure) of polyvinyl alcohol fiber (prototype 7) coated with a silver coating containing silver sulfate and hydroxypropylcellulose (HPC) according to the method of the present invention. ). In this image, the silver particles are encapsulated by the HPC in the silver coating, and it is clear that the silver coating covers the fibers, most clearly seen at the joint where the fibers intersect each other. FIG. 5B is a scanning electron micrograph image (1000 × magnification, BEC detection at 27 Pa pressure) of polyvinyl alcohol fiber (prototype 8) coated with a silver coating containing silver sulfate and hydroxypropyl cellulose (HPC) according to the method of the present invention. ). The image shows a cross-sectional view of the fibers where the silver particles are seen in white. As can be seen, silver particles are not present in the fiber. FIG. 6A is a cross-sectional view of a simple wound dressing according to one embodiment of the present invention. FIG. 6B is a cross-sectional view of an island dressing type wound dressing according to one embodiment of the present invention. FIG. 7A is a cross-sectional view of a border dressing type wound dressing according to one embodiment of the present invention. FIG. 7B is a cross-sectional view of a wound dressing according to one embodiment of the present invention.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS In general, the present invention relates to methods for preparing absorbable antimicrobial wound dressings, antimicrobial coating compositions used in those methods, and absorbable antimicrobials produced by those methods. Provide wound dressing.

I. Method for preparing an absorbent antibacterial wound dressing In one aspect, the invention provides a method for preparing an absorbent antibacterial wound dressing comprising the following steps: (a) in a solvent system comprising a non-aqueous solvent Preparing an antimicrobial coating composition by mixing an antimicrobial agent and one or more polymers, and (b) a wound dressing comprising the antimicrobial coating composition of step (a) and an absorbent fiber or absorbent particles Contacting the substrate, and (c) drying the product of step (b).

  In some embodiments, the contacting step (b) is performed using a slot die, foulard, or kiss coating. In some embodiments, the contacting step (b) is performed using slot die coating. In some embodiments, the contacting step (b) is performed using a fullered coating. In some embodiments, the contacting step (b) is performed using kiss coating.

  In some embodiments, the drying step (c) is performed by passing the wound dressing substrate through a hot air convection oven or over a hot plate. In some embodiments, the drying step (c) is performed by passing the wound dressing substrate through a hot air convection oven. In some embodiments, the drying step (c) is performed by passing the wound dressing substrate over a hot plate.

  In some embodiments, the method further comprises subjecting the wound dressing substrate to ethylene oxide sterilization after being dried in step (c). In some embodiments, ethylene oxide sterilization is performed according to standard methods ISO 11 135-1, ISO / TS 111135-2: 2008, or ISO 11135: 2014.

  Suitable wound dressings (including suitable substrates and absorbent fibers or absorbent particles), as well as suitable antimicrobial agents, polymers, and non-aqueous solvents include those described below.

A. Wound dressing matrix The wound dressing matrix may comprise absorbent fibers, absorbent particles, or combinations thereof. In some embodiments of the present invention, the wound dressing substrate is a wound dressing substrate that is at least 1 times its own weight as measured by EN 13726-1: 2002 (“Free swell absorptive capacity”). It has a free swelling absorption capacity corresponding to the maximum absorption capacity. For example, in some embodiments, the wound dressing matrix has a free swell absorption capacity, corresponding to the maximum absorption capacity of the wound dressing matrix, at least three times its own weight as measured by EN 13726-1: 2002. For example, in some embodiments, the wound dressing matrix has a free swell absorption capacity, corresponding to the maximum absorption capacity of the wound dressing matrix, at least five times its own weight as measured by EN 13726-1: 2002. For example, in some embodiments, the wound dressing matrix has a free swell absorption capacity that corresponds to the maximum absorption capacity of the wound dressing matrix at least 10 times its own weight as measured by EN 13726-1: 2002. For example, in some embodiments, the wound dressing matrix has a free swell absorption capacity, corresponding to the maximum absorption capacity of the wound dressing matrix, at least 15 times its own weight as measured by EN 13726-1: 2002. For example, in some embodiments, the wound dressing matrix has a free swell absorption capacity that corresponds to the maximum absorption capacity of the wound dressing matrix at least 20 times its own weight as measured by EN 13726-1: 2002. For example, in some embodiments, the wound dressing matrix has a free swell absorption capacity that corresponds to the maximum absorption capacity of the wound dressing matrix at least 25 times its own weight as measured by EN 13726-1: 2002. In some embodiments, the substrate comprises absorbent fibers. In some embodiments, the absorbent fibers are in the form of a nonwoven material. In some embodiments, the substrate comprises absorbent particles. In some embodiments, the absorbent particles are dispersed within a foam (eg, but not limited to a polyurethane foam). In some embodiments, the substrate also includes non-absorbable fibers. In some embodiments, the absorbent fibers and / or absorbent particles are airlaid by spraying, needling, or carding with non-absorbent fibers.

  In some embodiments, the absorbent fibers or particles comprise a polymer. Non-limiting examples of suitable polymers include polyvinyl alcohol, polysaccharides, polyacrylic acid, polymethacrylic acid, and copolymers comprising two or more monomers selected from vinyl alcohol, acrylic acid, and methacrylic acid. . In general, any reference to a polymer or monomer herein should be understood to encompass salts of these polymers or monomers. In some embodiments, the absorbent fibers or particles comprise polyvinyl alcohol. In some embodiments, the substrate comprises an absorbent fiber comprising polyvinyl alcohol. For example, in some embodiments, the absorbent fibers are a plurality of fibers comprising polyvinyl alcohol, such as US 2013/0323195 and / or US 2013/0274415 (hereby incorporated by reference). May be included). In some embodiments, the absorbent fibers or particles comprise polyacrylic acid. In some embodiments, the absorbent fibers or particles comprise polymethacrylic acid. In some embodiments, the absorbent fibers or particles comprise a copolymer comprising two or more monomers selected from vinyl alcohol, acrylic acid, and methacrylic acid. In some embodiments, the absorbent fibers or particles comprise a polysaccharide. In some embodiments, the polysaccharide is selected from the group consisting of cellulosic polymers, alginate, alginic acid, amylopectin, amylose, beta-glucan, carrageenan, chitosan, gellan gum, gelatin, pectic acid, pectin, and xanthan gum. The In some embodiments, the absorbent fiber or absorbent particle comprises a cellulosic polymer. In some embodiments, the absorbent fibers or particles comprise carboxymethylcellulose. In some embodiments, the absorbent particles are superabsorbent particles. As used herein, the term “superabsorbent particle” means a particle capable of absorbing at least 10 times its own weight in distilled water. In some embodiments, the superabsorbent particles are poly-N-vinyl pyrrolidone, polyvinyl toluene sulfonate, polysulfoethyl acrylate, poly-2-hydroxyethyl acrylate, polyvinyl methyl oxazolidinone, polyacrylamide, polyacrylic acid, polymethacrylic acid. Acids or polysaccharides, polyacrylic acid, polyacrylamide, or copolymers or terpolymers of polymethacrylic acid. In some embodiments, the superabsorbent particles comprise polyacrylic acid.

  In some embodiments, the absorbent fibers or particles comprise a polymer that is cross-linked. In some embodiments, the absorbent fibers or particles comprise cross-linked polyvinyl alcohol. In some embodiments, the substrate comprises an absorbent fiber comprising cross-linked polyvinyl alcohol. In some embodiments, the absorbent fibers or particles are cross-linked by heat or chemical treatment. In some embodiments, the absorbent fibers or particles are crosslinked by heat. In some embodiments, the wound dressing matrix may comprise cross-linked absorbent fibers, wherein the cross-linked absorbent fibers form a swollen coherent gel upon absorption of liquid. Can do. Thereby, the wound dressing substrate can be coherently removed from the wound. In some embodiments, in accordance with the “Free Swell Absorption Capacity Method” (EN 13726-1), the wound dressing substrate in a wet state that has absorbed a maximum amount of 0.9 wt% saline is EN 29073-3: It has a tensile strength of at least 0.2 N / 2 cm as measured by 1992 (applied to a 20 mm wide specimen). For example, in some embodiments, the wound dressing substrate in a wet state is at least 0.4 N / 2 cm, such as at least 0.6 N / 2 cm or at least 0.8 N / 2 cm, as measured by EN 29073-3: 1992 Has a tensile strength of at least 1.0 N / 2 cm. In some embodiments, the wound dressing substrate in the wet state has a tensile strength as measured by EN 29073-3: 1992 of at least 2 N / 2 cm, such as at least 2.5 N / 2 cm. In some embodiments, the wound dressing substrate in the wet state has a tensile strength of at least 3 N / 2 cm, such as at least 3.5 N / 2 cm. In some embodiments, the wound dressing substrate in the wet state is at least 4 N / 2 cm, such as at least 4.5 N / 2 cm, such as at least 5 N / 2 cm or at least 6 N / 2 cm, as measured according to EN 29073-3: 1992. It has a tensile strength of at least 7 N / 2 cm or at least 8 N / 2 cm or at least 9 N / 2 cm. In some embodiments, the wound dressing substrate in the wet state is a tensile strength as measured according to EN 29073-3: 1992 of at least 10 N / 2 cm, such as at least 15 N / 2 cm, such as at least 20 N / 2 cm or at least 25 N / 2 cm. Have In some embodiments, the wound dressing substrate in the wet state has a tensile strength of 0.2-15 N / 2 cm as measured by EN 29073-3: 1992. In some embodiments, the wound dressing substrate in the wet state has a tensile strength of 0.2 to 10 N / 2 cm as measured according to EN 29073-3: 1992. In some embodiments, the wound dressing substrate in the wet state has a tensile strength of 0.2-5 N / 2 cm as measured by EN 29073-3: 1992. In some embodiments, the wound dressing substrate in the wet state has a tensile strength of 1-4 N / 2 cm as measured by EN 29073-3: 1992. As used herein, the term “wound dressing substrate in a wet state” should be understood as a wound dressing substrate moistened to maximum absorption capacity according to EN 13726-1: 2002 (“free swelling” method). It is. Accordingly, the tensile strength given herein refers to the tensile strength measured against such a wet wound dressing substrate.

Other Components Specific ratio-limiting examples of wound dressings according to embodiments of the present invention are shown in FIGS. 6A, 6B, 7A, and 7B. As generally described above, the wound dressing of the present invention includes a substrate (eg, 1 in FIG. 6A, 5 in FIG. 6B, 6 in FIG. 7A, and 10 in FIG. 7B). In some embodiments, the wound dressing further comprises an adhesive layer for adhering to the skin (eg, 2 in FIG. 6A, 4 in FIG. 6B, 9 in FIG. 7A, and 12 in FIG. 7B). In some embodiments, the adhesive layer is disposed on the bottom surface of the substrate. In some embodiments, the wound dressing further comprises a perforated film layer (eg, 8 in FIG. 7A, 11 in FIG. 7B). In some embodiments, the perforated film layer is disposed between the substrate and the adhesive layer. In some embodiments, the wound dressing further comprises a backing layer (eg, 3 in FIG. 6B, 7 in FIG. 7A). In some embodiments, the wound dressing according to the present invention is used in combination with a secondary dressing applied to the top of the wound dressing according to the present invention.

B. Antimicrobial Coating Composition As generally described above, the present invention provides an antimicrobial coating composition for coating a wound dressing substrate. In general, antimicrobial coating compositions contain an antimicrobial agent and one or more polymers in a solvent system that includes a non-aqueous solvent. The present invention also provides a method for producing an antimicrobial coating composition for coating a wound dressing substrate, comprising mixing an antimicrobial agent and one or more polymers in a solvent system comprising a non-aqueous solvent. Including a method.

  As used herein, the term “antibacterial coating composition” refers in that “antibacterial coating” refers to a mixture of an antibacterial agent and one or more polymers applied to a substrate and dried. Distinguished from the term "antimicrobial coating". Thus, the antimicrobial coating can be thought of as a residue remaining on the substrate after the antimicrobial coating composition is applied to the substrate, the substrate is dried, and the solvent is removed.

Antibacterial agent In some embodiments, the antibacterial agent comprises silver. In some embodiments, the silver is metallic silver. In some embodiments, the silver is a silver salt. In some embodiments, the silver salt is silver sulfate, silver chloride, silver nitrate, sulfadiazine silver, silver carbonate, silver phosphate, silver lactate, silver bromide, silver acetate, silver citrate, CMC silver, silver oxide . In some embodiments, the silver salt is silver sulfate.

  In some embodiments, the antimicrobial agent comprises iodine. In some embodiments, the iodine is povidone iodine, cadexomer iodine, triosin, or iodozyme.

  In some embodiments, the antimicrobial agent comprises a monoguanide or biguanide. In some embodiments, the monoguanide or biguanide is chlorhexidine digluconate, chlorhexidine diacetate, chlorhexidine dihydrochloride, polyhexamethylene biguanide (PHMB) or a salt thereof, or polyhexamethylene monoguanide (PHMG) or a salt thereof. . In some embodiments, the biguanide is PHMB or a salt thereof.

  In some embodiments, the antimicrobial agent comprises a quaternary ammonium compound. In some embodiments, the quaternary ammonium compound is cetylpyridinium chloride, benzethonium chloride, or poly-DADMAC.

  In some embodiments, the antimicrobial agent comprises triclosan, sodium hypochlorite, copper, hydrogen peroxide, xylitol, or honey.

  In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of less than 40% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount less than 35% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of less than 30% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount less than 25% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount less than 20% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount less than 15% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of less than 10% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount less than 5% w / w.

  In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 40% w / w. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 35%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 30%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 25%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 20%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 15%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 10%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 5%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.1% to 1%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 0.5% to 3%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 1% to 40%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 5% to 40%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 10% to 40%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 15% to 40%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 20% to 40%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount from 25% to 40%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 30% to 40%. In some embodiments, the antimicrobial agent in the antimicrobial coating composition is present in an amount of 35% to 40%.

In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount less than 30 mg / cm ² . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount less than 25 mg / cm ² . In some embodiments, the antimicrobial agent in the wound dressing matrix is present in an amount less than 20 mg / cm ² . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount less than 15 mg / cm ² . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount less than 10 mg / cm ² . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount less than 5 mg / cm ² . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount less than 1 mg / cm ² . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount less than 0.5 mg / cm ² .

In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~30mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~35mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~30mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~25mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~20mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~15mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~10mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.01mg / cm 2 ~5mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.05mg / cm 2 ~3mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.05mg / cm 2 ~1mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing ^{substrate, 0.1mg / cm 2 ~1mg / cm} 2, for example, present in an amount of ^{0.1mg / cm 2 ~0.5mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.1mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{0.5mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{1mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{5mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{10mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{15mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{20mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{25mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{30mg / cm 2 ~40mg / cm 2} . In some embodiments, the antimicrobial agent in the wound dressing substrate is present in an amount of ^{35mg / cm 2 ~40mg / cm 2} .

Polymer In some embodiments, the one or more polymers in the antimicrobial coating composition are from the group consisting of cellulosic polymers, neutral poly (meth) acrylate esters, polyvinyl pyrrolidone, polyvinyl polypyrrolidone, and combinations thereof. Selected.

  In some embodiments, the one or more polymers in the coating composition are selected from cellulosic polymers. In some embodiments, the one or more polymers in the coating composition are from hydroxypropylmethyl-cellulose (HPMC), hydroxypropylcellulose (HPC), methylcellulose (MC), ethylcellulose (EC), and combinations thereof. The cellulosic polymer selected. In some embodiments, one of the one or more polymers in the coating composition is hydroxypropyl cellulose. In some embodiments, two of the polymers in the coating composition are hydroxypropyl cellulose and ethyl cellulose.

  In some embodiments, at least one of the one or more polymers in the antimicrobial coating composition is a neutral poly (meth) acrylate ester. In some embodiments, at least one of the one or more polymers in the coating composition is a methyl methacrylate / ethyl acrylate copolymer (eg, EUDRAGIT polymer).

  In some embodiments, at least one of the one or more polymers in the antimicrobial coating composition is water soluble. As used herein, a “water-soluble polymer” is soluble in water at a concentration of at least 1 gram / liter at 25 degrees Celsius. As used herein, a “water-insoluble polymer” dissolves in water at a concentration of 1 gram / liter or less at 25 degrees Celsius. In some embodiments, the one or more polymers in the antimicrobial coating composition comprises a mixture of at least one water soluble polymer and at least one water insoluble polymer.

  In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 30% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 20% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 10% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 5% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 4% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 3% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 2% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount less than 1% w / w.

  In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount from 0.5% to 30% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount from 0.5% to 20% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount of 0.5% to 10% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount from 0.5% to 5% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount from 0.5% to 4% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount from 0.5% to 3% w / w. In some embodiments, each of the one or more polymers in the antimicrobial coating composition is present in an amount of 1% to 2% w / w.

  In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 50-1500 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 300-1500 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 500-1500 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 800-1500 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 800-900 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 800 to 1,000 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 800 to 1,200 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 1,000 to 1,200 kDa. In some embodiments, the one or more polymers in the antimicrobial coating composition have an average molecular weight of 1,100 to 1,200 kDa.

Non-aqueous solvent In general, the antimicrobial coating composition comprises a non-aqueous solvent. In some embodiments, the non-aqueous solvent comprises a polar protic solvent. In some embodiments, the polar protic solvent comprises an alcohol. In some embodiments, the polar protic solvent comprises a C _1-4 alkyl alcohol. In some embodiments, the polar protic solvent comprises methanol, ethanol, n-propanol, isopropanol, n-butanol, or s-butanol. In some embodiments, the polar protic solvent comprises ethanol.

  In some embodiments, the antimicrobial coating composition comprises water. In some embodiments, the antimicrobial coating composition comprises less than 50% w / w water. In some embodiments, the antimicrobial coating composition comprises less than 40% w / w water. In some embodiments, the antimicrobial coating composition comprises less than 30% w / w water. In some embodiments, the antimicrobial coating composition comprises less than 20% w / w water. In some embodiments, the antimicrobial coating composition comprises less than 15% w / w water. In some embodiments, the antimicrobial coating composition comprises less than 10% w / w water. In some embodiments, the antimicrobial coating composition comprises less than 5% w / w water. In some embodiments, the antimicrobial coating composition comprises less than 1% w / w water. In some embodiments, the coating composition includes only trace amounts of water.

  In some embodiments, the antimicrobial coating composition comprises 1% to 50% w / w water. In some embodiments, the antimicrobial coating composition comprises 1% to 40% w / w water. In some embodiments, the antimicrobial coating composition comprises 1% to 30% w / w water. In some embodiments, the antimicrobial coating composition comprises 1% to 20% w / w water. In some embodiments, the antimicrobial coating composition comprises 1% to 10% w / w water. In some embodiments, the antimicrobial coating composition comprises 10% to 50% w / w water. In some embodiments, the antimicrobial coating composition comprises 10% to 40% w / w water. In some embodiments, the antimicrobial coating composition comprises 10% to 30% w / w water. In some embodiments, the antimicrobial coating composition comprises 10% to 20% w / w water. In some embodiments, the antimicrobial coating composition comprises 20% to 50% w / w water. In some embodiments, the antimicrobial coating composition comprises 20% to 40% w / w water. In some embodiments, the antimicrobial coating composition comprises 20% to 30% w / w water. In some embodiments, the antimicrobial coating composition comprises 30% to 50% w / w water. In some embodiments, the antimicrobial coating composition comprises 30% to 40% w / w water. In some embodiments, the antimicrobial coating composition comprises 40% to 50% w / w water.

Method for preparing an antimicrobial coating composition In some embodiments, the present invention is a method for manufacturing an antimicrobial coating composition for coating a wound dressing substrate, comprising a non-aqueous solvent A method is provided comprising mixing an antimicrobial agent and one or more polymers in a solvent system. Suitable antimicrobial agents, polymers and non-aqueous solvents include those described in the embodiments herein.

  In some embodiments, the method for preparing the antimicrobial coating composition comprises the following steps: (1) adding one or more polymers to a solvent system comprising a non-aqueous solvent; and (2) step. Adding an antimicrobial agent to the mixture obtained from (1).

  In some embodiments, (1) a mixture of one or more polymers in water is added to a non-aqueous solvent; and (2) a mixture of antimicrobial agents in the non-aqueous solvent is obtained from step (1). Added to the mixture. In some embodiments, the water in step (1) is heated. In some embodiments, the water in step (1) is heated such that the mixture in step (1) is a suspension of one and more polymers in water. In some embodiments, the non-aqueous solvent in steps (1) and (2) is the same.

  In some embodiments, a mixture of one or more polymers and antimicrobial agent in water is added to a non-aqueous solvent. In some embodiments, the water is heated so that the mixture is a suspension.

  In some embodiments, one or more polymers are added to a mixture of antimicrobial agents in a solvent system that includes a non-aqueous solvent. In some embodiments, one or more polymers are added to a mixture of antimicrobial agents in a non-aqueous solvent.

  In some embodiments, (1) one or more polymers are added to a non-aqueous solvent; and (2) an antimicrobial agent is added to the mixture resulting from step (1).

  In some embodiments, the mixture of antimicrobial agents in the non-aqueous solvent is added to the mixture of one or more polymers in the non-aqueous solvent. In some embodiments, the non-aqueous solvent in both solutions is the same.

  In some embodiments, the water in any of these methods is heated to 40-70 degrees Celsius. In some embodiments, the water is heated to 60 degrees Celsius.

  In some embodiments, the method further comprises increasing the viscosity of the mixture. In some embodiments, the viscosity of the mixture is increased by mixing for at least 10, 20, 30, 40, 50, or 60 minutes. In some embodiments, the viscosity of the coating composition is at least 100 centipoise as measured according to the viscosity method disclosed below (see Example 7). In some embodiments, the viscosity of the coating composition is 100-100000 centipoise, such as 5000-50000 centipoise, such as 5000-30000 centipoise or 10000-20000 centipoise, as measured according to the viscosity method disclosed below. (See Example 7).

II. Absorbent antimicrobial wound dressing In another aspect, the present invention provides an absorbent antimicrobial wound dressing, wherein the absorbent antimicrobial wound dressing comprises the following steps: (a) an antimicrobial agent in a solvent system comprising a non-aqueous solvent And an antimicrobial coating composition by mixing one or more polymers, and (b) an antimicrobial coating composition of step (a) and a wound dressing substrate containing absorbent fibers or particles And (c) drying the product of step (b).

  In yet another aspect, the present invention provides an absorbent antibacterial wound dressing, wherein the absorbent antibacterial wound dressing is coated with an absorbent fiber or an antibacterial coating containing an antibacterial agent and one or more polymers. Including a substrate containing absorbent particles, wherein the one or more polymers are a group consisting of cellulosic polymers, neutral poly (meth) acrylate esters, poly-vinyl pyrrolidone, polyvinyl polypyrrolidone, and combinations thereof Selected from. As used herein, the term “absorbent fiber or absorbent particle coated with an antimicrobial coating” refers to an absorbent fiber having some antimicrobial coating associated with at least a portion of its surface. Or an absorptive particle is meant. It does not require a complete or uniform coating of absorbent fibers or absorbent particles. Indeed, in some embodiments, the wound dressing substrate of the present invention comprises (a) an absorbent fiber (or absorbent particle) in which no antimicrobial coating amount is present on the surface, and (b) a portion of the surface. May comprise a mixture with absorbent fibers (or absorbent particles) associated with the antimicrobial coating. To illustrate this, scanning electron microscope images of several exemplary wound dressing substrates of the present invention are provided in FIGS. 5A and 5B.

  As shown in FIG. 5B, the antibacterial agent of the wound dressing of the present invention (here embodied by silver particles displayed in white) does not penetrate into the fibers of the matrix, but rather simply on the surface of the fibers. Is arranged.

  The invention is also described according to the following embodiments:

Embodiment 1: A method for preparing an absorbable antimicrobial wound dressing comprising:
(A) preparing an antimicrobial coating composition by mixing an antimicrobial agent and one or more polymers in a solvent system comprising a non-aqueous solvent;
(B) contacting the antimicrobial coating composition of step (a) with a wound dressing substrate containing absorbent fibers or particles; and (c) drying the product of step (b).
Including a method.

  The method according to the first embodiment, wherein the one or more polymers are selected from the group consisting of cellulosic polymers, neutral poly (meth) acrylate esters, polyvinylpyrrolidone, polyvinylpolypyrrolidone, and combinations thereof. .

  The method of the previous embodiment, wherein the absorbent fiber comprises polyvinyl alcohol.

  The method of the previous embodiment, wherein the polyvinyl alcohol is crosslinked.

  The method of any one of the previous embodiments, wherein said absorbent fiber comprises a cellulosic polymer.

  The method of the previous embodiment, wherein the absorbent fibers comprise carboxymethylcellulose.

  The method of any one of the previous embodiments, wherein the one or more polymers in the antimicrobial coating composition have an average molecular weight of 50-1500 kDa.

  The method of any one of the previous embodiments, wherein said one or more polymers in said antimicrobial coating composition is a cellulosic polymer.

  The cellulose in which the one or more polymers in the antibacterial coating composition are selected from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropyl-cellulose (HPC), methylcellulose (MC), and ethylcellulose (EC). The method of any one of the previous embodiments, wherein the method is a polymer based.

  The method of the previous embodiment, wherein the one or more polymers in the antimicrobial coating composition comprises hydroxypropylcellulose (HPC).

  The method of any one of the previous embodiments, wherein the antimicrobial agent comprises silver.

  The method of the previous embodiment, wherein the antibacterial agent is silver oxide or a silver salt.

  The previous embodiment, wherein the silver salt is selected from the group consisting of silver sulfate, silver chloride, silver nitrate, silver sulfadiazine, silver carbonate, silver phosphate, silver lactate, silver bromide, silver acetate, and silver citrate The method described in 1.

  The method of any one of the previous embodiments, wherein said non-aqueous solvent comprises a polar protic solvent.

  The method of the previous embodiment, wherein the polar protic solvent comprises an alcohol.

The method of the previous embodiment, wherein the alcohol comprises a C _1-4 alkyl alcohol.

The method of the previous embodiment, wherein the C _1-4 alkyl alcohol is methanol, ethanol, n-propanol, isopropanol, n-butanol, or s-butanol.

The method of the previous embodiment, wherein the C _1-4 alkyl alcohol is ethanol.

Step (a) includes the following substeps:
(1) adding one or more polymers to a solvent system comprising a non-aqueous solvent; and (2) adding an antibacterial agent to the mixture obtained from substep (1);
A method according to any one of the previous embodiments comprising:

  The method of any one of the previous embodiments, wherein step (b) is performed using a slot die, a fullard, or a kiss-coating.

  Absorbable antimicrobial wound dressing prepared according to the method of any one of the preceding embodiments.

  An absorbent antimicrobial wound dressing comprising a substrate containing absorbent fibers or absorbent particles coated with an antimicrobial agent and an antimicrobial coating containing one or more polymers, wherein the one or more polymers are An absorptive antimicrobial wound dressing selected from the group consisting of cellulosic polymers, neutral poly (meth) acrylate esters, polyvinyl pyrrolidone, polyvinyl polypyrrolidone, and combinations thereof.

  The wound dressing according to the previous embodiment, wherein the absorbent fibers comprise polyvinyl alcohol.

  The wound dressing according to the previous embodiment, wherein the polyvinyl alcohol is crosslinked.

  The wound dressing according to any one of the previous “wound dressing” embodiments, wherein the absorbent particles comprise polyacrylic acid.

  The wound dressing according to any one of the previous “wound dressing” embodiments, wherein the absorbent fibers comprise a cellulosic polymer.

  The wound dressing according to the previous embodiment, wherein the absorbent fibers comprise carboxymethylcellulose.

  The wound dressing according to any one of the previous “wound dressing” embodiments, wherein the one or more polymers in the antimicrobial coating have an average molecular weight of 50-1500 kDa.

  The wound dressing according to any one of the previous “wound dressing” embodiments, wherein the one or more polymers in the antimicrobial coating is a cellulosic polymer.

  The one or more polymers in the antibacterial coating is a cellulosic polymer selected from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), methylcellulose (MC), and ethylcellulose (EC). The wound dressing according to any one of the preceding “wound dressing” embodiments.

  The wound dressing according to any one of the previous “wound dressing” embodiments, wherein the one or more polymers in the antimicrobial coating comprises hydroxypropylcellulose (HPC).

  The wound dressing according to any one of the previous “wound dressing” embodiments, wherein the antimicrobial agent comprises silver.

  The wound dressing according to the previous embodiment, wherein the antibacterial agent is silver oxide or silver salt.

  The previous embodiment, wherein the silver salt is selected from the group consisting of silver sulfate, silver chloride, silver nitrate, silver sulfadiazine, silver carbonate, silver phosphate, silver lactate, silver bromide, silver acetate, and silver citrate Wound dressing as described in.

  A process for preparing an antimicrobial coating composition comprising mixing antimicrobial agent and one or more polymers in a solvent system comprising a non-aqueous solvent.

The mixing step (s) includes the following:
(1) adding one or more polymers to a solvent system comprising a non-aqueous solvent; and (2) adding an antimicrobial agent to the mixture obtained from step (1);
A process as described in the previous embodiment, comprising:

  The process of the previous two embodiments, wherein the antimicrobial agent comprises silver.

  The process of the previous embodiment, wherein the silver is silver oxide or a silver salt.

  The previous embodiment, wherein the silver salt is selected from the group consisting of silver sulfate, silver chloride, silver nitrate, silver sulfadiazine, silver carbonate, silver phosphate, silver lactate, silver bromide, silver acetate, and silver citrate The process described in

  Any of the preceding five embodiments, wherein the one or more polymers are selected from the group consisting of cellulosic polymers, neutral poly (meth) acrylate esters, polyvinylpyrrolidone, polyvinylpolypyrrolidone, and combinations thereof. The process according to one.

  The process of any one of the previous six embodiments, wherein the cellulosic polymer is hydroxypropylcellulose.

  The process of any one of the preceding seven embodiments, wherein said non-aqueous solvent in steps (1) and (2) comprises an alcohol.

  The process of the previous embodiment, wherein the non-aqueous solvent in steps (1) and (2) comprises ethanol.

(3) treating the mixture obtained from step (2) to increase its viscosity;
The process of any one of the previous nine embodiments, further comprising:

  The process of the previous embodiment, wherein step (3) comprises mixing the mixture obtained from step (2) for at least 60 minutes.

  The process of any one of the preceding 11 embodiments, wherein the amount of hydroxypropylcellulose in the antimicrobial coating composition is 1.0-1.5% w / w.

  Process according to any one of the preceding 12 embodiments, wherein the amount of water in the antimicrobial coating composition is 1% to 20% w / w.

  The process of any one of the preceding 13 embodiments, wherein the amount of water in the antimicrobial coating composition is less than 15% w / w.

  The process of any one of the preceding 14 embodiments, wherein the amount of antimicrobial agent in the antimicrobial coating composition is at least 0.1% w / w.

  The process of any one of the previous 15 embodiments, wherein the amount of antimicrobial agent in the antimicrobial coating composition is 0.1% to 40% w / w.

  An antimicrobial coating composition manufactured by the process of any one of the preceding 16 embodiments.

Example 1. Preparation of antimicrobial coating composition Silver sulfate (3.6 grams; commercially available from Sigma-Aldrich) is added to 190 proof ethanol (about 100 grams out of a total of 300 grams) in a beaker, after which the mixture is added to the rotor / The mixture was stirred for 10 minutes at 11000 rpm using a stator mixer. 65 degrees Celsius water (35 grams, 10% w / w of total weight of total mixture) is added to hydroxypropylcellulose (HPC, 4.3 grams; commercially available from Ashland) in a beaker until a mixture is obtained Turned for a few seconds. The beaker was immediately mounted under an overhead stirrer equipped with a dissolver blade, after which the stirrer was started. The ethanol / silver sulfate mixture was then carefully added to the mixing beaker. The sulfuric acid residue was rinsed into a beaker with the remainder of ethanol (about 200 grams). The combined ethanol / water / silver sulfate / HPC mixture was mixed for at least 60 minutes and the mixing speed was increased stepwise to 50-2000 rpm as the viscosity increased.

Example 2 Application to substrate and drying The antimicrobial coating composition from Example 1 is coated on silicone release paper (commercially available from POLY SLIK® Loparex). A nonwoven substrate (crosslinked PVA fibers; 250 gsm) (commercially available from Exufiber® Molnlycke Health Care) was pressed against the antimicrobial coating on the release layer using roller weights (2, 2 kg) Therefore, the antimicrobial coating was transferred to a nonwoven substrate. Thereafter, the nonwoven fabric substrate was removed from the release paper, transferred onto a hot plate (80 ° C.), and dried for 2 minutes with the dry surface facing the hot plate side. The same procedure was then repeated on the opposite side of the nonwoven substrate so that both sides of the product were coated.

Example 3 Prototypes for testing A number of prototypes, 1-8, shown in Table 1 below, were prepared. Prototype 2 was prepared according to Example 1, then Example 2. Prototype 3 was prepared according to Examples 1 and 2, with the exception that different concentrations of HPC and / or silver sulfate were used as listed in Table 1. Prototype 1 containing a silver coating without HPC was prepared by first preparing a silver coating composition according to Example 1 but without HPC, followed by the nonwoven substrate (same as Example 2) with a silver coating composition ( Dipped in a suspension of silver sulfate in ethanol). Here, the silver coating composition was constantly stirred with a spatula to avoid silver sulfate settling. The nonwoven substrate was dried on a hot plate (80 ° C.) for about 10 minutes until dried. Prototypes 4, 5 and 6 were prepared according to Example 1 and Example 2 (as shown in Table 1) with the following exceptions: (i) Nonwoven substrate (40 gsm) (Fibrella® 2000 Suominen Corporation, Helsinki, Commercially available from Finland) was used to prepare prototype 5; and a foam substrate (1.5 mm thick) (commercially available from Mepilex® Transfer, Molnlycke Health Care) was used to prepare prototype 6. (Ii) different concentrations of HPC and silver sulfate; and (iii) the silver coating composition was applied only to one side of the prototype 4, 5 and 6 substrates (non-adhesive foam side). In prototypes 7 and 8, the silver sulfate coating composition prepared according to Example 1 at the HPC and silver sulfate concentrations specified in Table 1 was applied to the substrate using slot die coating followed by drying in a hot air convection oven. I let you. Note that the HPC concentrations listed in Table 1 refer to the concentration of HPC in the coating composition prepared according to Example 1, ie, not the actual HPC concentration in the dried product. Should. The amount of silver (Ag ⁺ ) given in Table 1 is calculated by weighing the substrate before applying the silver coating composition followed by weighing the coated substrate (before its drying). Thus, the amount of silver coating composition captured by the substrate can be calculated, and the amount of silver (Ag ⁺ ) per unit area can be determined given a known silver concentration.

Example 4 Silver Sulfate Release Silver sulfate release from prototypes 1-3 was measured by immersing a round specimen (10 cm ² radius) in a USP bath vessel containing deionized water (70 ml, 32 ° C.). The paddle rotation speed was set to 125 rpm and a 1 ml sample was extracted after 5 hours. The concentration of silver sulfate in the extracted sample was analyzed using Inductively coupled plasma optical emission spectroscopy (ICP-OES). Silver is measured at wavelengths of 328.068 nm and 338.289 nm in axial mode, where 328.068 is used for quantification and 338.289 nm is used to detect interference. Each sample is measured in triplicate. FIG. 1 shows the total amount of silver released in 5 hours. As seen in FIG. 1, a nonwoven substrate (eg, Prototype 3) coated with a silver coating composition having a high concentration of HPC is compared to Prototype 2 with less HPC, or Prototype 1 without HPC. , With lower total silver emissions. Thus, this result shows that the silver release can be controlled by adjusting the amount of HPC in the coating composition.

Example 5 FIG. Wound dressing substrate discoloration reduction Prototypes 4-6 were tested for discoloration due to the presence of silver salt. Prototypes 4-6 (ca. 100-150 cm ² ) were subjected to a 55 ° C. and 80% RH test environment (Oven VC 0020 from Votsch Industritechnik), thereby accelerating the aging process. Measure color at different time points (on the coated surface of each prototype 4-6) according to ASTM D 2244-11, corresponding to the respective substrate of each prototype tested, but without the silver coating The change in color (dE) was calculated relative to a reference sample (not subjected to the test environment). FIG. 4 shows the color change observed in prototypes 4-6. As can be seen in FIG. 4, prototype 4 comprising a non-woven PVA substrate (Exufiber®) has prototype 5 (Fibrella® 2000 substrate) and prototype 6 (Mepilex® Transfer foam substrate) and In comparison, it showed a more reduced color change.

Example 6 Scanning electron image of the wound dressing substrate Scanning electron microscope images of the wound dressing substrate were obtained using a low vacuum SEM. Two types of detectors are used: secondary electron (SE) -detector (labeled LSEI = low vacuum secondary electron image) and backscattered electron (BEC) detector (labeled BEC = backscattered electron composition). By vacuum impregnating the specimen of prototype 8 in epoxy and then creating a smooth surface by grinding and ion polishing, the fiber cross section shown in FIG. 5B is produced. In the photograph of FIG. 5B, a heavy substance such as silver is displayed in white.

Example 7 Method for Measuring Viscosity The viscosity of a test mixture, such as an antimicrobial coating composition, is measured using a Brookfield Viscometer Instrument Model LVF. If the molecular weight of the polymer, such as HPC, in the antimicrobial coating composition is known, Table 2 below provides guidance for using the Brookfield viscometer spindle and spindle rotation. The viscosity of the test mixture (25 ° ± 0, 2 ° C.) is measured by inserting an appropriate Brookfield viscometer spindle into the test mixture and then starting the spindle rotation. Spin the test mixture for 3 minutes and stop the instrument before taking a reading. The reading is multiplied by a factor (provided by the device) corresponding to the speed and spindle used. The result is the viscosity of the test mixture in centipoise.

Claims (17)

A method for preparing an absorbent antibacterial wound dressing comprising:
(A) preparing an antimicrobial coating composition by mixing an antimicrobial agent and one or more polymers in a solvent system comprising a non-aqueous solvent;
(B) contacting the antimicrobial coating composition of step (a) with a wound dressing substrate containing absorbent fibers or particles; and (c) drying the product of step (b).
Including a method.   The method of claim 1, wherein the one or more polymers are selected from the group consisting of cellulosic polymers, neutral poly (meth) acrylate esters, polyvinyl pyrrolidone, polyvinyl polypyrrolidone, and combinations thereof.   The method of Claim 1 or Claim 2 in which the said absorptive fiber contains polyvinyl alcohol.   The method according to any one of claims 1 to 3, wherein the polyvinyl alcohol is crosslinked.   The method according to any one of claims 1 to 4, wherein the one or more polymers in the antimicrobial coating composition is a cellulosic polymer.   The cellulosic system in which the one or more polymers in the antimicrobial coating composition are selected from the group consisting of hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), methylcellulose (MC), and ethylcellulose (EC). 6. Process according to any one of claims 1 to 5, which is a polymer, preferably hydroxypropylcellulose (HPC).   7. A method according to any one of claims 1 to 6, wherein the antimicrobial agent comprises silver, preferably silver oxide or a silver salt.   8. A method according to any one of claims 1 to 7, wherein the non-aqueous solvent comprises a polar protic solvent, preferably an alcohol. Process according to claim 8, wherein the alcohol comprises a C _1-4 alkyl alcohol, preferably methanol, ethanol, n-propanol, isopropanol, n-butanol, or s-butanol, preferably ethanol.   Absorbable antimicrobial wound dressing prepared according to the method of any one of claims 1-9.   An absorbent antimicrobial wound dressing comprising a substrate containing absorbent fibers or absorbent particles coated with an antimicrobial agent and an antimicrobial coating containing one or more polymers, wherein the one or more polymers are An absorptive antimicrobial wound dressing selected from the group consisting of cellulosic polymers, neutral poly (meth) acrylate esters, polyvinyl pyrrolidone, polyvinyl polypyrrolidone, and combinations thereof.   The wound dressing according to claim 11, wherein the absorbent fiber comprises polyvinyl alcohol.   The wound dressing according to claim 12, wherein the polyvinyl alcohol is cross-linked.   The wound dressing according to claim 11, wherein the absorbent particles comprise polyacrylic acid.   15. A wound dressing according to any one of claims 11 to 14, wherein the one or more polymers in the antimicrobial coating is a cellulosic polymer.   The one or more polymers in the antibacterial coating are selected from the group consisting of hydroxypropyl methylcellulose (HPMC), hydroxypropyl-cellulose (HPC), methylcellulose (MC), and ethylcellulose (EC). The wound dressing according to any one of claims 11 to 15, which is preferably hydroxypropylcellulose (HPC).   The wound dressing according to any one of claims 11 to 16, wherein the antimicrobial agent comprises silver, preferably silver oxide or a silver salt.